Effect of the structure of dietary epoxylignan on its cytotoxic activity: relationship between the structure and the activity of 7,7′-epoxylignan and the introduction of apoptosis by caspase 3/7

<p>We compared the cytotoxic activities of dietary epoxylignans and their stereoisomers and found (−)-verrucosin, which is (7<i>S</i>,7′<i>R</i>,8<i>R</i>,8′<i>R</i>)-7,7′-epoxylignan, to be the most cytotoxic epoxylignan against HeLa cells (IC<sub>50</sub> = 6.6 μM). On the other hand, the activity was about a factor of 10 less against HL-60. In this research on the relationship between the structure and cytotoxic activity of (−)-verrucosin <b>13</b>, the 7-(4-methoxyphenyl)-7′-(3,4-dimethoxyphenyl) derivative <b>60</b>, for which the activity (IC<sub>50</sub> = 2.4 μM) is three times greater than (−)-verrucosin <b>13,</b> was discovered. The induction of apoptosis by caspase 3/7 was observed upon treatment with the (−)-verrucosin derivative.</p> <p>3′,4,4′-Trimethoxy-7,7′-epoxylignan showed highest IC<sub>50</sub> value (2.4 μM) in this structure–cytotoxic activity relationship experiment of 7,7′-epoxylignan. The IC<sub>50</sub> value of natural (−)-verrucosin was 6.6 μM.</p>